RESUMO
RATIONALE: The motor stimulant effects of the selective dopamine D2 receptor agonist, (+)-4-propyl-9-hydroxynaphthoxazine (PHNO), develop both tolerance and sensitization depending on circadian rhythms and time of day. Daytime tolerance can be transiently reversed by stress. Given that only tolerance develops when rats are kept under constant light conditions, it seems plausible that the pineal hormone melatonin may determine the circadian rhythm in tolerance and sensitization. OBJECTIVE: The effects of pinealectomy on the development of sensitization and stress-induced reversal of tolerance to sensitization to the motor stimulant effects of PHNO were determined. METHODS: Sprague-Dawley rats were pinealectomized or given sham operations and administered continuously with PHNO (5 microg/h) via subcutaneously implanted mini-pumps. Injections of 2-iodo-melatonin were subsequently administered to determine if sensitization to PHNO could be reinstated in the pinealectomized animals, assuming that sensitization would be reduced. RESULTS: Pinealectomy did not influence circadian rhythms in the development of sensitization and tolerance to PHNO. Pinealectomy blocked the motor activation effects of "injection-stress", and this effect was reinstated by treatment with 2-iodo-melatonin. CONCLUSIONS: Melatonin is not involved in the development of sensitization or tolerance to the behavioral effects of PHNO. However, melatonin modulates the stress-induced motor activity responses.